The NHGRI Bioinformatics and Scientific Programming Core actively supports the research being performed by NHGRI investigators by providing expertise and assistance in bioinformatics and computational analysis. The Core facilitates access to specialized software and hardware, develops generalized software solutions that can address a variety of questions in genomic research, develops database solutions for the efficient archiving and retrieval of experimental and clinical data, disseminates new software and database solutions to the genome community at-large, collaborates with NHGRI researchers on computationally-intensive projects, and provides educational opportunities in bioinformatics to NHGRI Investigators and trainees. Scientific projects completed in 2008-2009 include the design of the Homeodomain Resources Web site, analysis of sequence conservation between the 3 UTRs of orthologous human and chicken genes, identification of putative orthologs of ATAD5 and generation of a multiple sequence alignment, mapping of hundreds of thousands of zebrafish ear-specific MPSS tags to various zebrafish sequence databases, re-annotation of custom zebrafish oligonucleotide arrays, identification of fixed differences between human and three primates over 70 genomic regions, and assignment of the ancestral and derived state to SNPs from the same regions;analysis of a translocation breakpoint, extraction of upstream sequence for 700 mouse genes and their orthologs from chicken, human, and zebrafish;the update and release of a Web site for an <I>in situ</I>gene expression image database, annotation of a microarray platform from GEO with RefSeqs, genomic coordinates, and SNPs;identification and analysis of GEO datasets containing MMP8 gene expression data, and long-term follow-up on SIV retroviral integration sites in the rhesus macaque. Ongoing scientific projects include a redesign of the Histone Sequence Database, analysis of sequence traces to detect mutations in putative oncogenes in tumor samples, development of a Web-based prenatal survey, adaptation of traditional paper-based survey techniques for Web-based deployment, development of a Web site and database of hematologically important mutations, characterization of large exons in vertebrate, invertebrate, and plant genomes, ongoing updates and improvements to the Breast Cancer Information Core (BIC), development of a method to map zebrafish retroviral integration sites using Illumina sequence tags, prediction of gene regulatory regions in select zebrafish genes, mapping of 22-mers from the CFTR UTRs to the human genome, allowing for mismatches, development of a Web-based system for administering a cancer risk perception study, analysis of survey reports and Web behavior data, development of a customized SQL database for storing and computing on large numbers of records for canine genotypes, phenotypes, sequences, variations, sample data and pedigree data;development of various Perl scripts for data re-formatting, evolutionary analysis of the Magoh gene, identification of SNPs present in a list of 250,000 exons, development of an informational Web site for pigment cell genes, annotation of putative binding sites in a set of conserved and non-conserved non-coding elements for transcription factors that function in selected conditions, collation of multi-center survey data to study association between glucocerebrosidase mutations and Parkinsonism, compilation of a non-redundant list of the genomic coordinates of all human RefSeq genes, comparison of the integration profiles of the MLV and CATPAC retroviral vectors, and analysis of sequence traces to detection mutations for the zebrafish TILLING project.